AB0903 Dual Immunomodulatory Therapies in Psoriatic Disease
Authors: S. Sundanum, A. Gorman, D. Veale, C. Orr, L. O’neill
Journal: Annals of the Rheumatic Diseases (2022)

Background Since the advent of numerous biologic therapies and small molecular drugs targeting specific cytokines and signalling pathways; the management of patients with psoriatic arthritis (PsA) has significantly improved. However, at least 40% of PsA patients exhibit an incomplete or failure to respond to these treatments. While the outcomes of patients with psoriasis (Pso) has dramatically improved with monoclonal antibody therapies targeting IL-23 and IL-17A; achieving a measurable low disease activity state such as minimal disease activity (MDA) for musculoskeletal manifestations of psoriatic disease is infrequent. Given the complex and heterogeneity of signalling pathways, cytokines and cell types resulting in synovio-entheseal disease in PsA; new treatment strategies must be evaluated to induce deep and sustainable clinical responses in all the phenotypic domains of psoriatic disease (cutaneous, synovium, entheseal and axial). (1) In patients who do not achieve remission in all clinical domains on a biologic monotherapy or combination of a biologic therapy with an oral synthetic agent; dual targeted anti-cytokines strategies or combined biologic with a targeted oral small molecule are a possible treatment option. Objectives To describe a series of four patients with recalcitrant psoriatic disease and failure to respond to previous treatment regimens who were successfully treated with dual immunomodulatory therapies. Methods Patients on dual immunomodulatory therapies attending our department were prospectively followed and clinical response monitored. Results: Table 1. Age/gender Diagnosis prior therapies combination therapy dose adverse events Case 1 49/ Male PsA + PsO Methotrexate, adalimumab, etanercept, infliximab, golimumab, certolizumab, ustekinumab, secukinumab, ixekizumab Baracitinib + infliximab 4mg OD + 5mg/kg Q8W None Case 2 51/ Male PsA + PsO Methotrexate, etanercept, adalimumab, ustekinumab, infliximab, secukinumab, apremilast, ixekizumab, brodalumab, guselkumab Adalimumab + guselkumab 40mg QoW +100mg Q8W None Case 3 51/ Female PsA + PsO Methotrexate, sulphasalazine, etarnercept, certolizumab, leflunomide, infliximab, adalimumab, secukinumab, ustekinumab, tofacitinib, abatacept, baracitinib Adalimumab + tofacinitib 40mg QoW + 5mg BD None Case 4 39/ Male PsA +PsO Methotrexate, etanercept, ustekinumab, adalimumab, secukinumab, ixekizumab, sulphasalazine Ixekizumab + baracitinib 80mg Q4W+ 4mg OD None Figure 1. Mini-Arthroscopy of left knee for Case 3 prior to starting dual immunomodulator therapy. (A ) Macroscopic aspects of synovitis (B ) Synovium vascularization Conclusion Multiple pathways and mediators are responsible for the initiation of and sustained joint inflammation and damage seen in PsA. A phase II trial of ABT-122, a biologic engineered to target both TNF and IL-17A showed statistically significant superior efficacy outcomes at multiple time points based on ACR50, ACR70 and psoriasis outcome measures (PASI75/PASI90) when compared to adalimumab, with similar safety profile.(2) Safety concerns such as infectious risks are important considerations with such strategies; however, the targeted second-generation anti-cytokine biologics and targeted JAK-I have exhibited improved safety profiles.(3) In our small case series, patients have not, to date, experienced adverse events of combination therapy. References [1]Haberman RH, Castillo R, Scher JU. Induction of remission in biologic-naive, severe psoriasis and PsA with dual anti-cytokine combination. Rheumatology. 2021;60(7):e225-e6. [2]Mease PJ, Genovese MC, Weinblatt ME, Peloso PM, Chen K, Othman AA, et al. Phase II Study of ABT-122, a Tumor Necrosis Factor– and Interleukin-17A–Targeted Dual Variable Domain Immunoglobulin, in Patients With Psoriatic Arthritis With an Inadequate Response to Methotrexate. Arthritis &amp; Rheumatology. 2018;70(11):1778-89. [3]Scher JU, Ogdie A, Merola JF, Ritchlin C. Moving the Goalpost Toward Remission: The Case for Combination Immunomodulatory Therapies in Psoriatic Arthritis. Arthritis &amp; Rheumatology. 2021;73(9):1574-8. Disclosure of Interests None declared